Oral anti-inflammatory action of NPC 18884, a novel bradykinin B-2 receptor antagonist

This study describes the anti-inflammatory actions of NPC 18884, a non-pept ide bradykinin B-2 receptor antagonist in bradykinin and carrageenan-induce d inflammation in the mouse model of pleurisy. The selectivity of NPC 18884 was assessed in the pleurisy caused by histamine, substance P and des-Arg( 9)-bradykinin. NPC 18884 given intraperitoneally or orally inhibited bradyk inin-induced leukocytes influx (ID50 value of 63 nmol/kg and 141 nmol/kg, r espectively). The NPC 18884 also inhibited the exudation induced by bradyki nin (P < 0.05). NPC 18884 given either intraperitoneally or orally caused d ose-dependent inhibition of the exudation and total and differential cell c ontent caused by intrapleural injection of carrageenan (1%, assessed 4 h af ter), with mean ID50 values of 132 and 295 nmol/kg, respectively. The NPC 1 8884 actions installs rapidly (0.5 h), lasted for up to 4 h and were select ive for the bradykinin B-2 receptors; at similar doses it had no significan t effect against the inflammatory responses induced by des-Arg(9)-bradykini n, histamine or substance P. These results indicate that the novel non-pept ide bradykinin B-2 receptor antagonist, NPC 18884, exhibited selective intr aperitoneal and oral anti-inflammatory properties when assessed in the infl ammatory reaction induced by bradykinin and carrageenan in the mice model o f pleurisy. (C) 1998 Elsevier Science B.V. All rights reserved.